title: The effect of transcutaneous application of carbon dioxide (CO₂) on skeletal muscle.
abstract: In Europe, carbon dioxide therapy has been used for cardiac disease and skin problems for a long time. However there have been few reports investigating the effects of carbon dioxide therapy on skeletal muscle. Peroxisome proliferators-activated receptor (PPAR)-gamma coactivator-1 (PGC-1α) is up-regulated as a result of exercise and mediates known responses to exercise, such as mitochondrial biogenesis and muscle fiber-type switching, and neovascularization via up-regulation of vascular endothelial growth factor (VEGF). It is also known that silent mating type information regulation 2 homologs 1 (SIRT1) enhances PGC-1α-mediated muscle fiber-type switching. Previously, we demonstrated transcutaneous application of CO(2) increased blood flow and a partial increase of O(2) pressure in the local tissue known as the Bohr effect. In this study, we transcutaneously applied CO(2) to the lower limbs of rats, and investigated the effect on the fast muscle, tibialis anterior (TA) muscle. The transcutaneous CO(2) application caused: (1) the gene expression of PGC-1α, silent mating type information regulation 2 homologs 1 (SIRT1) and VEGF, and increased the number of mitochondria, as proven by real-time PCR and immunohistochemistry, (2) muscle fiber switching in the TA muscle, as proven by isolation of myosin heavy chain and ATPase staining. Our results suggest the transcutaneous application of CO(2) may have therapeutic potential for muscular strength recovery resulting from disuse atrophy in post-operative patients and the elderly population.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueha
authors.forename: Yoshitada
authors.initials: Y
authors.lastname: Sakai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Niikura
authors.forename: Sang Yang
authors.initials: SY
authors.lastname: Lee
authors.forename: Akihiro
authors.initials: A
authors.lastname: Koh
authors.forename: Takumi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miwa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009133:Muscular Atrophy / Q000188:drug therapy; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D002245:Carbon Dioxide; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D018995:Myosin Heavy Chains